This invention relates to methods of coating the lumenal surface of a blood vessel, or other tissue cavity, and to compositions suitable for use in same.
Various surgical and percutaneous therapies have been developed to reopen blocked channels, conduits, and other lumens, to remove diseased tissue, and to implant substitute tissue, or components thereof. While these therapies are effective, they often simultaneously injure cells or cellular components of the manipulated tissues.
The responses to injuries resulting from therapeutic interventions can cause complications that undo the beneficial effect of the intervention, or create new problems. For example, percutaneous transluminal angioplasty can open obstructed atherosclerotic arteries. However, the balloon-mediated stretch and crush injury to the arterial wall can lead to proliferation of the smooth muscle cells of the media of the artery, resulting in reclosure of the artery (xe2x80x9crestenosisxe2x80x9d) over the following months. This is observed in at least one-third of arteries treated. Another example is in the formation of adhesions after surgery, in which post-operative events result in the formation or proliferation of adventitious tissue that binds internal body surfaces together, causing discomfort, organ malfunction and potential morbidity and mortality. This can occur in many tissues and organs, including the intestine, the peritoneum, the heart, the pericardium, lungs, pleura, etc.
Various interventions have been proposed to minimize such problems. These include the use of stents and coatings in arteries (Slepian, in xe2x80x9cPolymeric Endoluminal Pavingxe2x80x9d Cardiology Clinics 12(14) (Nov. 1994), Slepian, et al, Circulation 88(4):part 2, 1-319 (1993), Hill-West, et al, Proc. Natl. Acad. Sci. USA 91:5967 (1994), U.S. Pat. No. 5,213,580, U.S. Pat. No. 5,800,538). In addition, the use of coatings, gels and fabrics can be used to prevent abdominal and pelvic adhesions (Hill-West et al, Obst. Gyne. 83:59 (1994)). Many of these treatments are administered after the injury has occurred, whether as a result of balloon angioplasty or otherwise, allowing the injured cells to initiate the series of processes involved in clotting, complement activation, and cellular response to release of cytokines, inducers of proliferation, and other biologically active molecules. It is difficult to stop these complex, interrelated processes once they have begun.
The present invention relates to methods, and compositions suitable for use therein, that minimize the reaction of cells and tissues, and of cells nearby or adjacent to them, to a subsequent injury.
The present invention provides, in one embodiment, a solution to the problem of restenosis following angioplasty. Specifically, the invention provides a method for endoluminal coating that involves application of a material to the interior surface of the involved blood vessel. The present approach is not limited to use in connection with restenosis, however, and can also be effectively employed in any hollow organ to provide local structural support, a smooth surface, improved flow and sealing of lesions. In addition, the coating material can incorporate therapeutic agents such as drugs or cell regeneration factors to accelerate healing processes. Such material with incorporated therapeutic agents can be effectively used to coat surgically or traumatically formed lumens in normally solid organs as well as the native or disease generated lumens of hollow or tubular organs.
Objects and advantages of the present invention will be clear from the description that follows.